Light entering the mammalian eye activates a neural pathway independent of the classical visual system, serving to regulate circadian rhythms. This neural pathway's response to light varies according to environmental context and thus, the non-image forming visual system represents an attractive model system of neural plasticity. Seasonal changes in photoperiod provide a rich example of how photic history can markedly change circadian regulation by light. Specifically, prior entrainment to a short winter-like photoperiod results in an approximately two-fold greater maximal phase shift as compared to relatively longer summer days (Goldman and Elliott, 1988;Evans et al., 2004). Despite this significant effect of photoperiod, surprisingly little has been done to follow-up on those findings. Recent preliminary work confirms the photoperiodic influence on circadian responsiveness and further demonstrates an increased sensitivity for phase advances in animals previously entrained to a short photoperiod, further refining our understanding of how photoperiod modulates photic response. By testing a variety of circadian outputs across a range of irradiances, we aim to determine whether photoperiodic history influences threshold, sensitivity, rate of increase, and/or maximal response to light. We plan to examine behavioral phase shifting, melatonin suppression and various biochemical markers in order to ultimately identify the level of regulation by which prior photic history modulates sensitivity to light for circadian input. Wheel-running activity rhythms will be employed to assess phase, nocturnal melatonin suppression will be measured via radioimmunoassay of pre- and post-light pulse plasma levels, and immunocytochemistry techniques will be used to identify the molecular mechanisms responsible for the behavioral differences in sensitivity observed in studies conducted thus far. Once a full complement of data have been collected for each study, fluence-response curves for each group will be fit to a parametric model, the half-saturation constant (i.e. ED50) will be determined, and significant differences in the ED50 will reveal differences in sensitivity. Data from each group will be analyzed via ANOVA, and statistical differences between groups will be assessed with post-hoc tests and determined significant if p<0.05. The results of these projects should serve to further elucidate the neural mechanisms by which photic history modulates the potency of light for circadian regulation. PUBLIC HEALTH RELEVANCE: We aim to determine the environmental factors and neural mechanisms that influence sensitivity to light for regulation of circadian rhythms. Understanding how light sensitivity is controlled will help to identify potential underlying physiological abnormalities as well as ways in which light therapy may be optimized for treatment of affective disorders and circadian sleep disturbances.